Genome-wide identification of the targets for genetic manipulation to improve L-lactate production by Saccharomyces cerevisiae by using a single-gene deletion strain collection.

To identify genome-wide targets for gene manipulation for increasing L-lactate production in recombinant Saccharomyces cerevisiae strains, we transformed all available single-gene deletion strains of S. cerevisiae with a plasmid carrying the human L-lactate dehydrogenase gene, and examined L-lactate production in the obtained transformants. The thresholds of increased or decreased L-lactate production were determined based on L-lactate production by the standard strain in repetitive experiments. L-lactate production data for 4802 deletion strains were obtained, and deletion strains with increased or decreased L-lactate production were identified. Functional category analysis of genes whose deletion increased L-lactate production revealed that ribosome biogenesis-related genes were overrepresented. Most deletion strains for genes related to ribosome biogenesis exhibited increased L-lactate production in 200-ml batch cultures. We deleted the genes related to ribosome biogenesis in a recombinant strain of S. cerevisiae with a genetic background different from that of the above deletion strains, and examined the effect of target gene deletion on L-lactate production. We observed that deletion of genes related to ribosome biogenesis leads to increased L-lactate production by recombinant S. cerevisiae strains, and the single-gene deletion strain collection could be utilized in identifying target genes for improving L-lactate production in S. cerevisiae recombinant strains.